Method and system of diagnosing and treating neurodegenerative disease and seizures

Abstract

A method of distinguishing a subject with pre-clinical Alzheimer's disease from those with similar symptoms but other forms of dementia such as mild cognitive impairment. The blood RNA whole transcriptome profile of a subject with suspected pre-clinical Alzheimer's disease is obtained and analyzed against a reference blood RNA whole transcriptome profile from a subject with another form of dementia such as frontal temporal dementia, CADASIL or mild cognitive impairment (MCI). The blood RNA whole transcriptome profile includes the presence and quantitation of ncRNA. Methods to enhance treatment of epileptic seizures are also discussed.

What is claimed is: 
     
         1 . A method of pre-clinical detection for incipient neurodegenerative disease, comprising the steps of:
 extracting a whole blood sample from a subject;   preparing an RNA library from the whole blood sample;   sequencing the RNA library;   determining differential expression of a plurality of RNA sequences comprised within the RNA library, wherein the plurality of RNA sequences comprises non-coding RNA (ncRNA);   creating a blood RNA transcriptome profile based on the differential expression of the RNA sequences;   comparing the blood RNA transcriptome profile to a reference blood RNA transcriptome profile derived from a subject with neurodegenerative disease;   detecting incipient neurodegenerative disease based on the correspondence between the blood RNA transcriptome profile and the reference profile derived from a subject with neurodegenerative disease.   
     
     
         2 . The method of  claim 1 , wherein the neurodegenerative disease is Alzheimer's disease. 
     
     
         3 . The method of  claim 2 , further comprising the step of detecting pro-dromal Alzheimer's disease. 
     
     
         4 . The method of  claim 1 , wherein the subject is selected based on one or more characteristics selected from the group consisting of geographical location, race, sex, age, weight, height (BMI), blood pressure, heartrate, body temperature, medications, routine admission blood studies and drug screens. 
     
     
         5 . The method of  claim 1 , wherein the neurodegenerative disease is one or more selected from the group consisting of Huntington's disease, Parkinson's disease, trinucleotide repeat disorders (DRPLA, SBMA, SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, FRAXA, FXTAS, FRAXE, FRDA, DM1, SCA8, SCA12), amyotrophic lateral sclerosis and Batten disease. 
     
     
         6 . The method of  claim 1 , wherein the RNA library further comprises miRNA and mRNA. 
     
     
         7 . The method of  claim 1 , further comprising comparing the blood RNA transcriptome profile to a reference blood RNA transcriptome profile from a subject with a dementia selected from one or more of the group consisting of frontal temporal dementia, CADASIL and mild cognitive impairment (MCI). 
     
     
         8 . A method of enhancing treatment of preclinical Alzheimer's disease, comprising the steps of:
 extracting a whole blood sample from a subject;   preparing an RNA library from the whole blood sample;   sequencing the RNA library;   determining differential expression of a plurality of RNA sequences comprised within the RNA library, wherein the plurality of RNA sequences comprises non-coding RNA (ncRNA);   creating a blood RNA transcriptome profile based on the differential expression of the RNA sequences;   comparing the blood RNA transcriptome profile to a reference blood RNA transcriptome profile derived from a subject with preclinical Alzheimer's disease;   detecting preclinical Alzheimer's disease based on the correspondence between the blood RNA transcriptome profile and the reference profile derived from a subject with preclinical Alzheimer's disease;   treating the subject with a therapy for Alzheimer's disease.   
     
     
         9 . The method of  claim 8 , where the therapy for Alzheimer's disease comprises: administering cholinesterase inhibitors. 
     
     
         10 . The method of  claim 9 , wherein the cholinesterase inhibitors are selected from the group consisting of one or more of donepezil, rivastigimine and galantamine. 
     
     
         11 . A method of enhancing treatment of preclinical Parkinson's disease, comprising the steps of:
 extracting a whole blood sample from a subject;   preparing an RNA library from the whole blood sample;   sequencing the RNA library;   determining differential expression of a plurality of RNA sequences comprised within the RNA library, wherein the plurality of RNA sequences comprises non-coding RNA (ncRNA);   creating a blood RNA transcriptome profile based on the differential expression of the RNA sequences;   comparing the blood RNA transcriptome profile to a reference blood RNA transcriptome profile derived from a subject with preclinical Parkinson's disease;   detecting preclinical Parkinson's disease based on the correspondence between the blood RNA transcriptome profile and the reference profile derived from a subject with preclinical Parkinson's disease;   treating the subject with a therapy for Parkinson's disease.   
     
     
         12 . The method of  claim 11 , where the therapy for Alzheimer's disease comprises: administering one or more drugs selected from the group consisting of levodopa, carbidopa, dopamine agonists, catechol O-methyltransferase (COMT) inhibitors, anticholinergics, amantadine, aducanumab and monoamine oxidase type B (MAO-B) inhibitors. 
     
     
         13 . A method of enhancing treatment of epileptic seizures, comprising the steps of:
 extracting a whole blood sample from a subject;   preparing an RNA library from the whole blood sample;   sequencing the RNA library;   determining differential expression of a plurality of RNA sequences comprised within the RNA library, wherein the plurality of RNA sequences comprises non-coding RNA (ncRNA);   creating a blood RNA transcriptome profile based on the differential expression of the RNA sequences;   comparing the blood RNA transcriptome profile to a reference blood RNA transcriptome profile derived from a subject with an epileptic seizure;   detecting epileptic seizure based on the correspondence between the blood RNA transcriptome profile and the reference profile derived from a subject with epileptic seizure;   treating the subject with a therapy for epileptic seizure.   
     
     
         14 . The method of  claim 13 , wherein the subject has identified genetic descent of the patient being African and the identified gender of the patient being male. 
     
     
         15 . The method of  claim 13 , wherein the subject has identified genetic descent of the patient being African and the identified gender of the patient being female. 
     
     
         16 . The method of  claim 13 , wherein the subject has identified genetic descent of the patient being European and the identified gender of the patient being male. 
     
     
         17 . The method of  claim 13 , wherein the subject has identified genetic descent of the patient being European and the identified gender of the patient being female. 
     
     
         18 . The method of  claim 13 , wherein the subject has identified genetic descent of the patient being Asian and the identified gender of the patient being male. 
     
     
         19 . The method of  claim 13 , wherein the subject has identified genetic descent of the patient being Asian and the identified gender of the patient being female. 
     
     
         20 . The method of  claim 13 , wherein the treatment for epileptic seizures comprises: administering one or more drugs selected from the group consisting of brivaracetam, ezogabine, pregabalin, cannabidiol oral solution, felbamate, primidone, carbamazepine, fenfluramine, rufinamide, carbamazepine-XR, gabapentin, stiripentol, cenobamate, lacosamide, tiagabine hydrochloride, lamotrigine, clobazam, levetiracetam, topiramate, clonazepam, levetiracetam XR, topiramate XR, diazepam nasal, lorazepam, valproic acid, diazepam rectal, oxcarbazepine, vigabatrin, divalproex sodium-ER, phenobarbital, eslicarbazepine acetate, phenytoin and ethosuximide.